All of the long bones are developed through a process called endochondral bone formation, in which a growth plate determines the bone size and shapes. The hypertrophic chondrocyte is an important regulatory cell during endochondral bone formation, because bone lengthening is driven primarily by the rate of production of hypertrophic chondrocytes from proliferating chondrocytes. Disrupting this sequential progression of chondrocyte differentiation leads to pathological consequences such as chondrodysplasia. This morphogenic process is exquisitely regulated by tissues adjacent to the growth plate cartilage. One of these neighboring tissues is subchondral bone marrow at the base of the growth plate and adjacent to the hypertrophic zone. It produces a chemokine stromal cell derived factor (SDF-1), which maintains chondrocyte hypertrophy and stimulates matrix resorption. The long-term objective of this study is to analyze signaling mechanisms in regulating endochondral bone formation of growth plate cartilage by adjacent tissues. In particular, we will focus on chemokin regulation of cartilage matrix degradation in developing cartilage, based on our findings as follows. First, P38 MAPK activity correlates with chondrocyte differentiation; Second, specific expression of CXCR4 (receptor of SDF- 1) is found in hypertrophic chondrocytes; Third, SDF-1 induces hypertrophic phenotype of chondrocytes; Fourth, SDF-1 stimulates MMPs release and migration of chondrocytes; Finally, SDF-1 signaling in chondrocytes dependents on p38 activity. Our central hypothesis is that SDF-1 signaling plays a central role to control the pace of cartilage matrix resorption through p38 activity. To test this hypothesis systematically, we will determine whether stimulation of chondrocyte p38 activity by a chemokine SDF-1 leads to induction of matrix resorption and chondrocyte chemotaxis through releasing matrix metalloproteinases.